LIGHT, a new member of the TNF superfamily, and lymphotoxin alpha are ligands for herpesvirus entry mediator.
Herpes simplex virus (HSV) 1 and 2 infect activated T lymphocytes by attachment of the HSV envelope glycoprotein D (gD) to the cellular herpesvirus entry mediator (HVEM), an orphan member of the tumor necrosis factor receptor superfamily. Here, we demonstrate that HVEM binds two cellular ligands, secreted lymphotoxin alpha (LTalpha) and LIGHT, a new member of the TNF superfamily. LIGHT is a 29 kDa type II transmembrane protein produced by activated T cells that also engages the receptor for the LTalphabeta heterotrimer but does not form complexes with either LTalpha or LTbeta. HSV1 gD inhibits the interaction of HVEM with LIGHT, and LIGHT and gD interfere with HVEM-dependent cell entry by HSV1. This characterizes herpesvirus gD as a membrane-bound viokine and establishes LIGHT-HVEM as integral components of the lymphotoxin cytokine-receptor system.
Mauri
D N
DN
Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
Ebner
R
R
Montgomery
R I
RI
Kochel
K D
KD
Cheung
T C
TC
Yu
G L
GL
Ruben
S
S
Murphy
M
M
Eisenberg
R J
RJ
Cohen
G H
GH
Spear
P G
PG
Ware
C F
CF
D000595:Amino Acid Sequence; D001483:Base Sequence; D018259:Herpesvirus 1, Human / Q000276:immunology / Q000378:metabolism; D018258:Herpesvirus 2, Human / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D018124:Receptors, Tumor Necrosis Factor; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D012680:Sensitivity and Specificity; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000378:metabolism / Q000648:ultrastructure; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000378:metabolism
D008024:Ligands; D008233:Lymphotoxin-alpha; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; C506028:TNFRSF14 protein, human; C505914:TNFSF14 protein, human; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1